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Single-cell spatial transcriptomic profiling defines a pathogenic inflammatory niche in chronic active multiple sclerosis lesions - snRNA-seq

GSE301908 Homo sapiens (human) Single-nucleus RNA-seq 17 samples Submitted 2025/10/29 Platform GPL24676
At a glance

Single-nucleus RNA-seq · human · 17 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue).
Organism
Homo sapiens (human)
Samples
17 samples: 17 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Summary (written by the submitters)
Compartmentalized inflammation is considered a critical factor in driving the progression of multiple sclerosis (MS). Yet, the mechanisms sustaining its persistence remain poorly understood. A hallmark of this persistent and slowly evolving inflammatory process are chronic active MS lesions. In this study, we created a high-resolution, single-cell molecular and spatial atlas of chronic inflammation in MS.
Read the full summary ↓
To accomplish this, we combined single-nucleus RNA sequencing (snRNA-seq) with single-cell spatial transcriptomics using multiplexed error-robust fluorescence in situ hybridization (MERFISH) to examine MS lesions, specifically focusing on those exhibiting chronic active immune pathology characterized by lymphocyte presence. Our integrative profiling uncovered the molecular landscape of glial and immune cells, their disease-associated states, and the surrounding microenvironments. Within the lesion rim, we identified CD8+ T cell niches with inflamed, foamy microglia, characterized by an interferon response and dysfunctional lipid metabolism. To investigate the function of these microglia, we deleted ATP-binding cassette transporters A1 and G1 (ABCA1/G1) in microglia of mice and induced experimental autoimmune encephalomyelitis (EAE). Our findings revealed that inhibiting cholesterol efflux increased the formation of lipid-storing phagocytes, which actively drove inflammatory processes in EAE. Moreover, we found that pharmacologically targeting sterol metabolism presents a promising therapeutic strategy for mitigating inflammation in EAE. Thus, we have created a high-resolution map of immune niches in chronic active MS lesions, leading to the discovery of lipid-associated microglia as key drivers of neuroinflammation.
This dataset
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE301908_RAW.tar (it can run to tens of gigabytes).

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1287730 and SRA study SRP598916. Searching any of these in the dataset finder brings you back here.

Study design
17 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 17 sample titles: 17 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study
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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.